Human Immunodeficiency Virus (type-1) (HIV-1) belongs to retrovirus and a causative virus of Acquired Immunodeficiency Syndrome (AIDS). The pol gene of HIV-1 encodes three essential enzymes: reverse transcriptase (RT), protease (PR) and integrase (IN). Currently 21 FDA approved drugs targeting RT and PR are available and are administered in various combinations. The combination of highly active antiretroviral therapy (HAART) in compliant patients comes close to stopping virus evolution, however, eradication of the infection has not been achieved because of the persistence of latent HIV-1 in resting memory CD4+ T cells. Moreover, several factors including the emergence of multidrug-resistant HIV strains, drug toxicity, the patient's ability to adhere to the prescribed therapy and expensive medication have necessitated a reason to develop novel drugs, which target other viral replication processes.
HIV-1 integrase has emerged as an attractive target for antiretroviral drugs because of its crucial role in the viral replication processes. HIV-1 integrase catalyses two crucial steps required for the integration of viral DNA into the host chromosome. In the first step, while in the cytoplasm of an infected cell, integrase selectively cleaves two nucleotides (GT) from the 3′ terminal of the viral cDNA in a reaction known as 3′-processing. Immediately after translocation to the nucleus as a component of the pre-integration complex, integrase randomly inserts the viral cDNA into the host genome, and this reaction is referred to as strand transfer or integration. Over the past years several integrase inhibitors have been discovered, yet none of them reached the clinic.